Enzymes in the poly(ADP-ribose)polymerase (PARP) protein family participate in a number of cellular functions including assisting in the repair of DNA damage. Inhibiting PARP activity is a promising therapeutic approach to treatment of certain cancers. A number of PARP inhibitors are in clinical and preclinical stages as candidate drugs for treatments of ovarian, breast, colorectal, prostate and other cancers. A class of PARP inhibitors disclosed in U.S. Pub. No. 2010/0035883 includes (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one. Preclinical studies indicate that this compound may be a useful therapy for some cancer patients.
U.S. Pub. No. 2010/0035883 provides a synthesis of 5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one and chiral resolution of its (8S,9R) enantiomer. See, e.g., U.S. 2010/0035883, Examples 94 and 155, incorporated herein by reference in its entirety for all purposes. Additional methods of preparing the compound are described in WO 2011/097602. To move a drug candidate such as (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one to a viable pharmaceutical product, it can be important to understand whether the drug candidate has polymorph forms, as well as the relative stability and interconversions of these forms under conditions likely to be encountered upon large-scale production, transportation, storage and pre-usage preparation. The ability to control and produce a stable polymorph with a robust manufacturing process can be key for regulatory approval and marketing. Large scale production processes for high purity 5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one are sought, which is hampered by the fact that parameters affecting the stability of this compound are not known and polymorphic forms of the compound have not been available.